19.

Amines, Amides , Amino Acids and proteins

Naming

H H H
Amines H2N O
These end in –amine. H C C C NH2 If there is another
There is, however, rather confusingly CH C
priority functional group
two ways of using this suffix. H H H
as well as the amine H3C O H
The exam board tend to use the propylamine group then the prefix
common version where the name Or propan-1-amine 2-aminopropanoic acid.
amino is used.
stem ends in -yl propylamine.
The IUPAC version of the same
chemical is propan-1-amine. (This is
used in the same way as naming
alcohols)

If the amine is secondary and has two alkyl CH3CH2CH2NHCH3

groups attached to the nitrogen, then each N-methylpropylamine (common name)
chain is named and the smaller alkyl group N-methylpropan-1-amine (IUPAC name)
is preceded by an –N which plays the same
role as a number in positioning a side alkyl CH2 CH2
chain H3C NH CH3

Diethylamine (common name- does not use N if

In the common naming version if the chains are same length)
chain lengths are the same an –N is N-ethylethanamine (IUPAC name does still use N)
not used

CH3CH2 CH2 N CH3

If a tertiary amine similar rules apply,
and each alkyl side group is given an CH3
N N,N-dimethylpropylamine (common name)
N,N-dimethylpropan-1-amine (IUPAC name)

H H
N (CH2)6 N It could also be named
1,6-diaminohexane
H H
hexane-1,6-diamine

Amides

O Secondary and tertiary amides

Add –amide to the stem are named differently to show the O
name CH3 C two (or three) carbon chains.
NH2 The smaller alkyl group is
preceded by an –N which plays H3C CH2 C NH CH3
ethanamide the same role as a number in
N-methylpropanamide
positioning a side alkyl chain

O CH3
CH3 O CH3
H3C CH2 C N CH3
H3C CH C N CH3
N,N-dimethylpropanamide N,N,2-trimethylpropanamide

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Properties of Amines
Amines have a characteristic fishy smell H δ+
δ- δ+ δ-

Small amines can form hydrogen bonds with water and CH3 N H O
δ+
therefore can dissolve readily in water.
H
Base Properties
H δ+
Primary aliphatic amines act as Bronsted-Lowry bases because the lone
pair of electrons on the nitrogen is readily available for forming a dative CH3NH2 +H2O  CH3NH3+ +OH-
covalent bond with a H+ and so accepting a proton.

Primary aliphatic amines are stronger bases than ammonia as the alkyl
groups are electron releasing and push electrons towards the nitrogen NH3 (aq) +H2O (l)  NH4+(aq) +OH-(aq)
atom and so make it a stronger base.

Secondary amines are stronger bases than primary amines because they have more alkyl groups that are substituted onto
the N atom in place of H atoms. Therefore more electron density is pushed onto the N atom (as the inductive effect of alkyl
groups is greater than that of H atoms).
One might expect using the same trend that tertiary amine would be the strongest amine base but the trend does not hold.
The tertiary amines and corresponding ammonium salts are less soluble in water and this makes them less strong bases
than the secondary amines. (This point will not be examined)

Base strength of aromatic amines NH2

Primary aromatic amines such as phenylamine do not form basic solutions because the lone
pair of electrons on the nitrogen delocalise with the ring of electrons in the benzene ring. This
means the N is less able to accept protons. phenylamine

Reactions with acids

Amines as bases react with acids to form ammonium salts.

CH3NH2 (aq) +HCl (aq)  CH3NH3+Cl-(aq) Addition of NaOH to an ammonium salt
Methylamine methylammonium chloride will convert it back to the amine
2CH3NH2 (aq) +H2SO4 (aq)  (CH3NH3+)2 SO42- (aq)
These ionic salts will be solid crystals, if the
water is evaporated, because of the strong
The ionic salts formed in this reaction means that the ionic interactions.
compounds are soluble in the acid.
e.g. Phenylamine is not very soluble in water but
phenylammonium chloride is soluble

Making a basic buffer from an amine

Basic buffers can be made from combining a weak base with a salt of that weak base
e.g. Ammonia and ammonium chloride
Methylamine and methylammonium chloride
Ethylamine and ethylammonium chloride
Formation of complex ions
The lone pair of electrons on the nitrogen enable amines to act as ligands and form dative covalent bonds into
transition metal ions to form coloured complex ions.

4 CH3CH2NH2 + Cu(H2O)62+ [Cu(CH3CH2NH2)4(H2O)2] 2+ +4H2O

This is a similar ligand exchange reaction to the one where ammonia acts as the ligand

4NH3 + Cu(H2O)62+ [Cu(NH3)4(H2O)2] 2+ + 4H2O

light blue solution deep blue solution
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Reaction of primary Amines with halogenoalkanes forming secondary amines

Amines will react with halogenoalkanes in a similar way to the reaction of ammonia with
halogenoalkanes via a nucleophilic substitution reaction

2CH3CH2NH2+ CH3CH2Br CH3CH2NH2CH2CH3+ CH3CH2NH3Br

H
+
H3C C Br H3C CH2 NH2 CH2 CH3 Br -
H
:

CH3CH2NH2
+
H3C CH2 NH CH2 CH3 H3C CH2 NH CH2 CH3 + CH3CH2NH3Br
:NH2CH2CH3
Diethylamine
H

The secondary amine formed can also then react with more halogenoalkane to form a tertiary amine
and subsequently on to what is called a quaternary ammonium salt
Where RX is the haloalkane

H R R
H RX
RX RX
+
H N: R N: R N: R N R

R R R R

Reaction with primary amines with acyl chlorides

Change in functional group: acyl chloride  secondary amide

Reagent: primary amine
Forming Amides
Conditions: room temp.
Aliphatic amines and
RCOCl +2CH3NH2  RCONHCH3 + CH3NH3+Cl- phenylamine can react
with acyl chlorides to
form amides in a
O O
nucleophilic addition-
CH 3 + CH3NH3 Cl
+ -
CH3 C + 2CH3NH2  CH 3 C NH elimination reaction- see
chapter 15C for more
Cl N-methylethanamide details.

Paracetamol is made by the reaction of an aromatic amine with an

acyl chloride to produce an amide
O
CH3 C
Cl O
HO NH2 HO NH C CH3

Paracetamol

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The preparation of primary aliphatic amines
1. Forming a primary amine in a one step reaction of halogenoalkanes with ammonia

Primary amines can be formed by the nucleophilic substitution reaction between halogenoalkanes and ammonia in
a one step reaction. However, as the lone pair of electrons is still available on the N in the amine formed, the
primary amine can react in the same nucleophilic way in a successive series of reactions forming secondary, tertiary
amines and quaternary ammonium salts.
This is therefore not a good method for making a primary amine because of the further reactions. It would mean the
desired product would have to be separated from the other products.

CH3CH2Br + 2NH3  CH3CH2NH2 + NH4Br Ammonia dissolved in ethanol is the initial nucleophile
H H
+ In the first step of the mechanism the nucleophile
H3C C Br H3C C NH3 Br -
attacks the halogenoalkane to form an intermediate
H
3HN:
H
H H
+ In the second step of the mechanism a second
H3C C NH2 H3C C NH2 + NH4Br ammonia removes a proton from the
:NH3 intermediate (acts as base) to form the amine
H H H

Using an excess of ammonia can limit the further

subsequent reactions and will maximise the amount of
primary amine formed

2. Preparing Amines from Nitriles

Using the method above of reacting halogenoalkanes and ammonia is not an efficient method for preparing a
high yield of the primary amine because of the further substitution reactions that occur.
A better method is to use the following reactions
Step 1. convert halogenoalkane to nitrile by using KCN in aqueous ethanol (heat under reflux)

CH3CH2Br + CN-  CH3CH2CN + Br -

Step 2. reduce nitrile to amine by using LiAlH4 in ether or by reducing with H2 using a Ni catalyst

CH3CH2CN + 4[H] CH3CH2CH2NH2

A disadvantage of this method is that it is a two step reaction that may therefore have a low yield. Also
KCN is toxic.

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Reducing nitroarenes to aromatic amines
The nitro group on an arene can be reduced an amine group as follows

Reagent: Sn and HCl or Fe and HCl NO 2 NH2

Conditions: Heating + 6[H] + 2H2O
Mechanism:reduction

phenylamine
nitrobenzene

As the reaction is carried out in HCl the salt C6H5NH3+Cl- will be formed.
Reacting this salt with NaOH will give phenylamine.

The phenylamine formed in this reaction is best

separated from the reaction mixture by steam distillation.

Synthesis of azo dyes

Step 1: reaction of an aromatic amine with nitrous acid at Nitrous acid is generated in
<10 °C, forming a diazonium ion, situ from NaNO2/HCl.

NH2 NaNO2 + HCl <10oC Below 0oC the temperature is

+ too low and the reaction would
N N be too slow

diazonium ion If the diazonium ion is allowed to

heat above 10oC it reacts with water
to form phenol and N2 gas
C6H5NH2 + HNO2 + HCl C6H5N2+ Cl− + 2H2O
C6H5N2+ + H2O  C6H5OH + N2 + H+

Step 2: coupling of diazonium ion with a phenol under

alkaline conditions;

NaOH
+
N N + OH N N OH

4-hydroxyazobenzene
C6H5N2+ Cl− +C6H5OH  C6H5N2C6H4OH +HCl

Azo dyes are used for dyes, pigments and

colourings

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Addition Polymerisation

An addition polymer forms when unsaturated Poly(alkenes) are chemically inert due to the strong C-C
monomers react to form a polymer and C-H bonds and non-polar nature of the bonds and
Monomers contain C=C bonds therefore are non-biodegradable.

It is best to first draw out

O O O
the monomer with groups
of atoms arranged around H C NH2
C H C NH2
the double bond
H2C CH NH2
C C H C C H
e.g. For propenamide n
H H H H
Poly(ethenol) poly(propenamide)

H OH H OH
n C C H C C H The addition polymer poly(ethenol) has good solubility in
n water because it can form many strong hydrogen bonds
H H H H with water. The makes it a useful polymer for uses such
poly(ethenol) as soluble laundry bags and liquid detergent capsules
(liquitabs) .

Condensation Polymerisation
The two most common types of
condensation polymers are
polyesters and polyamides which
involve the formation of an ester
linkage or an amide linkage.
In condensation polymerisation there are two different monomers
that add together and a small molecule is usually given off as a
side-product e.g. H2O or HCl.
The monomers usually have the same functional group on both ends
of the molecule e.g. di-amine, di carboxylic acid, diacyl chloride.

Forming polyamide uses these reactions we met earlier in the course

Acyl chloride + Amine  amide + HCl Carboxylic Acid + Amine  amide + water

If we have the same functional group on each end of molecule we can make polymers so we have the
analogous equations:
diacyl dichloride + diamine  poly(amide) + HCl dicarboxylic acid + diamine  poly(amide) + water

Nylon 6,6 - a common polyamide

O O
O O H H
N (CH2)6 N
n C (CH2)4 C +n C (CH2)4 C N (CH2)6 N + 2n-1 H2O
H H
HO OH
hexanedioic acid Hexane-1,6-diamine H H
n
The 6,6 stands for 6 carbons in each of the monomers. Different length carbon chains produce different
polyamides
Kevlar- a common polyamide

O O
n HO2C CO2H + n H2N NH2 + 2n-1 H2O
N N C C
H H n

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Note on classification for condensation polymers
If asked for type of polymer: It is polyamide or polyester
Whereas type of polymerisation is condensation
It is also possible for polyamides and polyesters to form from one monomer, if that monomer
contains both the functional groups needed to react

O O O O
HO (CH2)3 C O (CH2)3 C O (CH2)3 C O (CH2)3 C
Cl
3 repeating units

O O O O
H2N C
N C N C N C
OH
H H H
3 repeating units

Chemical reactivity of condensation polymers The reactivity can be explained by the presence of
polyesters and polyamides can be broken down by polar bonds which can attract attacking species
hydrolysis and are, therefore, biodegradable such as nucleophiles and acids

Hydrolysis
Polyesters and polyamides can be hydrolysed by acid and alkali
The hydrolysis will result in the original monomers forming- although the carboxylic acid or amine group
will be in salt form depending on whether the conditions are alkaline or acidic

O O
O
+
HCl OH H 3N +
C (CH2)4 C N (CH2)6 N
HO
+ NH 3
H H O
n

NaOH O
-
-CO(CH2)4CONHC(CH3)2CH2O- - O
O + H2N
This polymer has both an amide and O
OH
ester link

Intermolecular bonding between condensation polymers chains

Polyesters have permanent dipole forces between the Cδ+=Oδ- groups in the different chains in
addition to the London forces between the chains.

Polyamides (and proteins) have hydrogen δ-

:

O Oδ- O
bonding between the lone pairs on oxygen in δ-
N C N C Nδ- C
Cδ+=Oδ- groups and the H in the Nδ- —Hδ+ δ+ δ+
H H δ+ H δ+
groups in the different chains.
There are also Permanent dipole-permanent
dipole forces because the polar C=O
:

O δ- Oδ- O
bond and polar C-N bond δ- δ-
N C N C N C
There are also London forces which are large δ+ δ+
because there are many electrons in the H H Hδ+
δ+
molecule
Polyamides will therefore have higher melting
points than polyesters.

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Amino Acids

The simplest amino acid is

General structure of an amino acid NH2 CH2 CO2H
glycine, where the R is an H
NH2 CH CO2H

R
The R group can be a variety of
different things depending on what
amino acid it is.

Naming amino acids

CO2H Some amino acids have an extra CO2H
You do not need to know any carboxylic acid or an amine
CH2 CH2
common names for the 20 group on the R group. These are
essential amino acids. We NH2 C CO2H classed as acidic or basic NH2 C CO2H
should, however, be able to H 2-aminobutanedioic acid (respectively) amino acids H
name given amino acids using Aspartic acid
IUPAC organic naming OH
CO2H
CH2
H C (CH2)4 NH2
NH2 CH2 CO2H NH2 C CO2H Lycine (basic)
H 2-amino-3-
H2N 2,6-diaminohexanoic acid
(2-)aminoethanoic acid
hydroxypropanoic acid

Zwitterions
R R
The no charge form of an amino acid never occurs. + -
The amino acid exists as a dipolar zwitterion. H2N C CO2H H3N C CO2
H H
Amino acids are often solids Zwitterion
The ionic interaction between zwitterions explains the relatively high melting points of amino acids as
opposed to the weaker hydrogen bonding that would occur in the no charge form.

Acidity and Basicity

The amine group is basic and the carboxylic acid group is acidic. Amino acids act as weak buffers and will
only gradually change pH if small
R OH- R H+ R amounts of acid or alkali are added to the
- + - +
H2N C CO2 H3N C CO2 H3N C CO2H amino acids.
+NH -CH -CO - + HCl  Cl- NH3+-CH2-CO2H
H H H 3 2 2
H+ OH-
+NH -CH -CO - + NaOH  NH2-CH2-CO2-Na+ +H2O
Species in Species in Species in 3 2 2
alkaline solution neutral solution acidic solution
High pH Low pH

-
The extra carboxylic acid or amine groups COO
on the R group will also react and change CH2 Aspartic acid in high pH
form in alkaline and acid conditions -
NH 2 C COO
H

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 Optical Activity
All amino acids, except
glycine, are chiral because
there are four different groups
H2N
around the C
They rotate plane polarised light.
Optical isomers have similar
H H
physical and chemical
properties, but they rotate
C C
CO2H HO2C plane polarised light in
NH2 different directions.
CH3 CH3

Proteins CH3

Proteins are polymers made from H3C CH3 S

combinations of amino acids. CH HS CH2
The amino acids are linked by peptide links,
CH3 O CH2 O CH2 O CH2 O
which are the amide functional group.
H N CH C N CH C N CH C N CH C O H
O O O H H H H
NH CH C NH CH C NH CH C

R R R

Dipeptides
Dipeptides are simple combination molecules of For any two different amino acids there are two possible
two amino acids with one amide (peptide) link. combinations of the amino acids in the dipeptide.

HO HO
HO
CH3 H
Can make CH3 H CH2 CH2 CH3
CH2 or
H2N C CO2H +
H2N C C N C CO2H H2N C C N C CO2H
H H2N C CO2H
H H H O H
O
H

O δ- O
Importance of hydrogen bonding in proteins
:

δ-
N CH C N CH C
The 3D arrangement of amino acids with the δ+
polypeptide chain in a corkscrew shape is held in δ+
H R H R
place by Hydrogen bonds between the H of –Nδ-
:

—Hδ+ group and the –O of Cδ+=Oδ- δ-

O O
δ-
N CH δ+ C N CH C

H R H R

Other reactions of amino acids

The carboxylic acid group and amine group in amino acids can undergo the usual reactions of these functional groups met
in earlier topics. Sometimes questions refer to these.
e.g. Esterification reaction
CH3 CH3 O
H+ +
H2N C CO2H + CH3OH H3N C C O CH3 + H2O

H H

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